DESCRIPTION: Based on their work and that of other laboratories, these investigators propose that hDlg is a component, possibly the essential nucleating agent, of a multi-protein complex of plasma membrane- associated signaling molecules. This hypothesis is based on the observed binding of hDlg sequences to APC, Abl, Crk, Lck, a new putative dual-specificity protein kinase called PBK1 (PDZ-Binding Kinase 1), T/SXV motif channel proteins, SH3-containing proteins, polyproline- containing proteins, and/or protein 4.1 oezrin. The proposed research will test this hypothesis by: (1) refining the map of interaction domains between hDlg and 4.1/ERM proteins and the role of this interaction in targeting to the membrane; (2) quantifying and refining the understanding of hDlg association with itself; (3) quantifying and refining the partners; and (4) assessing the implication of the PDZ- mediated association between hDlg and a putative kinase identified by a yeast two-hybrid screen. The long-term goal is to understand better the mode of action and biochemical characteristics of this tumor suppressor protein.